A large scale survey for hemoglobinopathies in China was undertaken involving about 120,000 individuals. Many abnormal hemoglobins and various types of Alpha and Beta thalassemia and HPFH heterozygotes were found among these subjects. This will provide us with material for the following studies: 1. We propose to study the incidence of the different types of Gamma chain (i.e. the A Gamma T, A Gamma I, G Gamma chains) and to determine their relative quantities in newborn babies of different Chinese populations and to analyze unusual Gamma chain variants and conditions characterized by unusual ratios between the normally occurring Gamma chains. 2. By mapping the Gamma-globin genes and related (i.e. Beta and Delta) genes of HPFH and Beta-thalassemia individuals using restriction endonucleases, useful information concerning the control of fetal hemoglobin synthesis in these disorders and perhaps also in normal conditions may be obtained. Analyses of the Gamma, Delta, Beta globin genes by restriction endonuclease mapping will be meaningful in the evaluation of the genetic basis of these disorders. 3. RNA and DNA analyses by RNA/cDNA hybridization and restriction endonuclease will provide the definitive methods for the determination of the Alpha-thalassemia types. The same methods will be used for the prenatal diagnosis of Hb H disease and Hb Bart's hydrops fetalis and for differentiation of the deletion types of Alpha-thalassemia from the nondeletion type. It seems almost certain that important information concerning the molecular basis of Alpha-thalassemia syndromes will be obtained. 4. Many hemoglobin variants have been found in China some having abnormal functional properties (Hb M, unstable hemoglobins, and some hemoglobins with abnormal O2 dissociation curves). Study of the structure and the function of these abnormal proteins will give a better understanding of the relationship between structural and functional relationships.